Details for Patent: 10,828,297

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Which drugs does patent 10,828,297 protect, and when does it expire?

Patent 10,828,297 protects AKYNZEO and is included in two NDAs.

This patent has sixty-nine patent family members in forty-two countries.

Summary for Patent: 10,828,297

Title:	Compositions and methods for treating centrally mediated nausea and vomiting
Abstract:	Provided are compositions and methods for treating or preventing nausea and vomiting in patients undergoing chemotherapy, radiotherapy, or surgery.
Inventor(s):	Fabio Trento, Sergio Cantoreggi, Giorgia Rossi, Roberta Cannella, Daniele Bonadeo
Assignee:	Helsinn Healthcare SA
Application Number:	US15/923,050
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,828,297
Patent Claim Types: see list of patent claims	Use; Delivery;

US Patent 10,828,297: Scope, Claims, Expiration Risk, and Patent Landscape for Akynzeo

US Patent No. 10,828,297 protects clinical use of intravenous or otherwise systemically administered netupitant and palonosetron, together with dexamethasone, to prevent chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic chemotherapy. The patent is directed to treatment outcomes and pharmacokinetic or pharmacodynamic exposure, not to a standalone chemical composition.

The claim set is commercially relevant to Akynzeo, Helsinn’s fixed antiemetic combination containing netupitant and palonosetron, including the intravenous formulation in which fosnetupitant is converted in vivo to netupitant. The principal enforcement issue is whether a competing product, label, or treatment protocol induces the claimed three-drug regimen and achieves the specified exposure or clinical results.

What drug and treatment regimen does US Patent 10,828,297 cover?

The patent covers prevention or treatment of acute and delayed chemotherapy-induced nausea and vomiting, or CINV, in a patient receiving highly emetogenic chemotherapy.

The core regimen requires:

Required element	Claim requirement
Patient	Subject receiving highly emetogenic cancer chemotherapy
NK1 antagonist	Netupitant
5-HT3 antagonist	Palonosetron
Corticosteroid	Dexamethasone
Clinical objective	Prevention of acute and delayed nausea and vomiting, complete response, no emesis, no rescue medication, or prevention of nausea
Administration	Claim 1 is not limited to intravenous administration; dependent claims add intravenous treatment
Exposure	Certain claims require blood levels equivalent to specified oral doses
Pharmacodynamic endpoint	At least 70% occupancy of striatal NK1 receptors 72 hours after administration

The independent claims are method claims:

• Claim 1 covers prevention of acute and delayed nausea and vomiting.
• Claim 2 covers achieving complete response during both phases.
• Claim 3 covers preventing nausea during both phases.

Claims 4 through 23 add intravenous administration, oral-dose-equivalent exposure, NK1 receptor occupancy, and specific treatment outcomes.

How broad are the independent claims?

Claims 1, 2, and 3 are broad in treatment objective but narrow in drug combination.

A direct infringement analysis would generally require proof that the accused regimen includes:

1. Netupitant or a product that produces therapeutically effective netupitant blood levels.
2. Palonosetron.
3. Dexamethasone.
4. Treatment of highly emetogenic chemotherapy.
5. The claimed prevention or response outcome.

The claims do not require a particular commercial product, vial, dosage form, excipient, infusion duration, or administration route unless a dependent claim is asserted. Claim 1 therefore reaches beyond the specific intravenous product described in dependent claims 4 through 6.

The claims also do not require that netupitant and palonosetron be administered in the same physical dosage form. A regimen using separate products could potentially fall within the independent claims if all other limitations are met.

What does “therapeutically effective blood levels” mean?

“Therapeutically effective blood levels” is a functional limitation. It requires that the administered regimen produce systemic concentrations capable of supporting the claimed antiemetic effect.

The term creates two issues:

• It may require clinical or pharmacokinetic evidence rather than merely proof that the active ingredients were administered.
• It may be interpreted in light of the specification, examples, pharmacokinetic data, and the disclosed relationship between intravenous administration and oral netupitant/palonosetron dosing.

A generic manufacturer could argue that its product produces different exposure levels, different timing, or a clinically distinct regimen. The patent holder would likely respond that the claim is directed to therapeutic exposure and outcome, not to a particular formulation.

Which dependent claims are most commercially important?

Claims 4 through 6 are the most relevant to intravenous Akynzeo-type products.

Claims 4, 13, and 19: intravenous pre-chemotherapy administration

These claims require an intravenous antiemetic regimen administered before chemotherapy. They are directed to the practical clinical use of an IV netupitant/palonosetron regimen.

The claims do not expressly require fosnetupitant. A product that administers netupitant directly could fall within the claim if such a product generated the required blood levels. A fosnetupitant product may also be relevant because fosnetupitant is converted to netupitant in the body.

Claims 5, 14, and 20: oral-dose-equivalent exposure

These claims require blood levels equivalent to exposure produced by:

• 50 to 500 mg of netupitant free base; and
• 0.075 to 1.0 mg of palonosetron hydrochloride administered orally.

This is an exposure-based limitation. It does not require the accused product to contain those exact quantities. The analysis would focus on bioequivalence or comparable pharmacokinetic exposure.

Claims 6, 15, and 21: specific exposure target

These claims narrow the exposure requirement to levels equivalent to:

• 300 mg of netupitant free base; and
• 0.56 mg of palonosetron hydrochloride administered orally.

This limitation closely tracks the oral Akynzeo dose while addressing an intravenous regimen. It is likely to be central in any patent dispute involving an IV combination product.

Claims 7, 16, and 22: NK1 receptor occupancy

These claims require netupitant to occupy at least 70% of the patient’s striatal NK1 receptors 72 hours after administration.

This is a pharmacodynamic limitation. It may be difficult to prove in routine clinical practice because direct measurement of striatal NK1 receptor occupancy generally depends on specialized imaging or validated pharmacodynamic modeling. It may nevertheless be relevant to infringement by equivalence or to validity disputes involving written description, enablement, definiteness, and experimental support.

Claims 8 through 11 and 17: treatment outcomes

These claims add one or more outcomes:

• Complete response.
• No emesis.
• No rescue medication.
• Prevention of nausea.

“Complete response” in CINV studies commonly means no emesis and no use of rescue medication during the relevant assessment period. The patent’s clinical definitions and specification would control the precise interpretation.

Claims 12, 18, and 23: independent effectiveness of netupitant

These claims state that netupitant blood levels are independently effective to prevent CINV, produce complete response, or prevent nausea.

These limitations may create a significant construction issue. They appear to distinguish the contribution of netupitant from the contribution of palonosetron. A challenger may argue that the claims require proof that netupitant alone, at the claimed blood level, independently produces the specified effect. Helsinn may argue that “independently effective” describes the pharmacological contribution of netupitant within the combination regimen rather than requiring monotherapy.

What product is commercially connected to the patent?

The patent is most closely connected to Akynzeo, marketed by Helsinn and approved by the FDA for prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy and moderately emetogenic cancer chemotherapy.

Akynzeo exists in relevant forms including:

Product	Active or converted active ingredients	Regulatory relevance
Oral Akynzeo capsule	Netupitant 300 mg and palonosetron 0.5 mg	Oral fixed-dose combination
Intravenous Akynzeo	Fosnetupitant, converted to netupitant, and palonosetron	IV pre-chemotherapy regimen
Dexamethasone coadministration	Separate corticosteroid regimen	Required by the asserted method claims

The intravenous product is particularly important because the claims expressly recite IV administration and exposure equivalent to oral netupitant/palonosetron dosing. The FDA prescribing information directs administration before chemotherapy and addresses dexamethasone use in the antiemetic regimen [FDA, 2024].

What is the Orange Book status of US Patent 10,828,297?

US Patent 10,828,297 is associated with the Akynzeo patent estate and is relevant to FDA-listed exclusivity analysis for the product. Orange Book treatment depends on the specific NDA, dosage form, and patent-use code submitted by the NDA holder.

For a small-molecule product, an Orange Book-listed method-of-use patent can require an ANDA applicant to:

• File a Paragraph IV certification challenging patent validity, enforceability, or infringement;
• Submit a section viii statement seeking approval for nonpatented uses; or
• Wait until patent expiry if the applicant does not challenge the listing.

The commercial effect of the listing depends on the patent-use code. If the listed use covers the primary FDA-approved CINV indication, a section viii carve-out may be difficult or commercially ineffective.

The patent does not create biologic exclusivity. Akynzeo is a small-molecule drug combination, so the relevant competitive pathway is an ANDA, not a biosimilar application under the Public Health Service Act.

When does US Patent 10,828,297 lose exclusivity?

The patent issued on November 10, 2020. Its exact expiration date must be determined from the full USPTO prosecution record, including:

• The earliest effective nonprovisional priority date;
• Patent term adjustment;
• Any terminal disclaimer;
• Continuation or divisional relationships;
• Patent term extension, if granted.

The claim text alone does not establish the enforceable expiration date. A business analysis should distinguish the nominal 20-year patent term from the adjusted expiration date shown in USPTO Patent Center and any FDA Orange Book entry.

The patent’s practical exclusivity may end earlier or later than the nominal date through:

• Invalidity litigation;
• A settlement with an ANDA applicant;
• A covenant not to sue;
• A license;
• A terminal disclaimer;
• A court ruling limiting the asserted claims.

What prior patents surround the Akynzeo patent estate?

The relevant estate is broader than US 10,828,297. It may include patents directed to:

1. Netupitant as an NK1 receptor antagonist.
2. Palonosetron as a 5-HT3 receptor antagonist.
3. The netupitant/palonosetron combination.
4. Oral fixed-dose formulations.
5. Intravenous fosnetupitant formulations.
6. Methods of preventing acute and delayed CINV.
7. Pharmacokinetic exposure and dosing.
8. Manufacturing and formulation processes.

The commercial patent landscape should therefore be separated into four layers:

Patent layer	Primary risk
Active-ingredient patents	Basic chemical or pharmaceutical protection
Combination patents	Netupitant plus palonosetron use or composition
Formulation patents	Oral capsule, IV solution, prodrug, excipient, stability, or reconstitution protection
Method-of-use patents	CINV prevention, dosing timing, exposure, receptor occupancy, or outcome

US 10,828,297 is principally a method-of-use and exposure patent. It is not, based on the supplied claims, a broad composition-of-matter patent covering netupitant or palonosetron.

Which companies could challenge the patent?

Potential challengers would be generic pharmaceutical companies developing:

• Oral netupitant/palonosetron capsules;
• IV fosnetupitant/palonosetron products;
• Separate netupitant and palonosetron products intended for combined use;
• Alternative NK1/5-HT3 combination products.

An ANDA applicant targeting the patented indication could use Paragraph IV certification. The likely defenses would include:

• No infringement because the proposed label omits dexamethasone or the patented use;
• No infringement because the product does not achieve the claimed exposure;
• Invalidity for anticipation;
• Obviousness based on known NK1 and 5-HT3 combination therapy;
• Lack of written description for the broad functional claims;
• Lack of enablement for the full range of exposure and clinical outcomes;
• Indefiniteness of “therapeutically effective blood levels,” “equivalent,” or “independently effective.”

Helsinn’s strongest infringement position would likely arise where a generic label expressly instructs use before highly emetogenic chemotherapy with dexamethasone and where the product’s pharmacokinetic profile corresponds to the claimed oral-dose-equivalent exposure.

What patent litigation and settlements affect the product?

The material litigation risk is likely to arise from ANDA filings against Akynzeo rather than from biosimilar litigation. A Paragraph IV action would trigger the Hatch-Waxman framework, including a potential 30-month stay of final ANDA approval if the NDA holder timely sues.

A settlement could establish:

• An agreed generic launch date;
• A license to one or more patents;
• A covenant covering specific dosage forms;
• A limitation to moderate-emetogenic chemotherapy;
• A carve-out for noninfringing uses;
• A royalty or supply arrangement.

Settlement analysis must be performed patent by patent. A settlement covering an oral formulation patent may not resolve exposure or IV method claims under US 10,828,297.

How strong is the patent estate?

US 10,828,297 has meaningful commercial scope but presents litigation vulnerabilities.

Strengths

• It covers the clinically important combination of netupitant, palonosetron, and dexamethasone.
• It reaches acute and delayed CINV.
• It includes IV administration and oral-dose-equivalent exposure.
• It covers functional clinical outcomes that may correspond closely to the approved label.
• The use of pharmacokinetic and receptor-occupancy limitations can distinguish the claims from generic antiemetic regimens that use different exposure profiles.

Vulnerabilities

• The core pharmacological combination may be challenged as obvious.
• “Therapeutically effective blood levels” may require fact-intensive proof.
• “Equivalent” exposure may raise definiteness and claim-construction disputes.
• The receptor-occupancy claims may be difficult to establish using ordinary clinical records.
• Method claims depend on conduct by physicians, hospitals, or patients.
• A generic applicant may attempt a label carve-out or design a regimen that avoids the claimed dexamethasone or highly emetogenic chemotherapy language.

The strongest claims for enforcement are likely claims 4 through 6, 13 through 15, and 19 through 21, because they map more directly onto an IV commercial product and specify administration and exposure. The broadest claims, 1 through 3, have greater reach but also create more substantial construction and validity disputes.

What generic launch scenarios exist?

Scenario	Commercial result
No ANDA challenge	Generic launch generally waits for patent and regulatory barriers to clear
Paragraph IV challenge with no settlement	Litigation may delay approval through the Hatch-Waxman stay
Paragraph IV settlement	Launch occurs on the negotiated date, subject to settlement terms
Section viii carve-out	Approval may proceed for nonpatented uses if the FDA accepts the carve-out
Alternative IV formulation	Product may avoid composition claims but still face method claims
Separate-component strategy	May avoid a fixed-dose composition claim but retain induced-infringement exposure
Different antiemetic combination	May avoid this patent while competing clinically with Akynzeo

What geographic coverage does the patent provide?

US Patent 10,828,297 provides rights only in the United States. It does not block products in Europe, Japan, Canada, or other markets.

International risk must be assessed through corresponding national applications and granted patents. The relevant questions include:

• Whether a counterpart was granted in each target jurisdiction;
• Whether the claims cover IV fosnetupitant or only netupitant exposure;
• Whether national patent offices allowed the clinical outcome limitations;
• Whether supplementary protection certificates or other term extensions apply;
• Whether local litigation or settlement terms affect launch timing.

What manufacturing and intellectual-property barriers remain?

Manufacturing barriers are separate from the method claims. An IV competitor may need to address:

• Fosnetupitant synthesis;
• Conversion to netupitant;
• Palonosetron stability;
• Sterile manufacturing;
• Reconstitution and administration;
• Impurity controls;
• Container-closure compatibility;
• Product stability and shelf life.

A competitor may avoid a formulation patent yet still face the method claims if its label directs the same regimen and its product produces the claimed exposure.

Key Takeaways

• US Patent 10,828,297 is primarily a method-of-use and pharmacokinetic patent.
• The core regimen combines netupitant, palonosetron, and dexamethasone for highly emetogenic chemotherapy.
• Claims 4 through 6, 13 through 15, and 19 through 21 are the most relevant to intravenous Akynzeo-type products.
• The patent does not, based on the supplied claims, broadly protect netupitant or palonosetron as chemical compositions.
• The principal generic challenge routes are Paragraph IV litigation, section viii carve-outs, and alternative dosing or labeling.
• The patent does not create biosimilar risk because Akynzeo is a small-molecule product.
• Exact patent expiration requires the USPTO term record, including priority, patent term adjustment, and any terminal disclaimer.
• The main validity issues are obviousness, written description, enablement, definiteness, and proof of claimed exposure or clinical outcomes.
• The commercial risk is highest for IV products that produce oral-dose-equivalent netupitant and palonosetron exposure and are labeled for use with dexamethasone before highly emetogenic chemotherapy.

FAQs

Does US Patent 10,828,297 cover oral Akynzeo?

Potentially, yes. The independent claims are not limited to intravenous administration. The dependent claims directed to IV administration do not restrict the broader independent claims. An oral product could face risk if its use satisfies all limitations, including the dexamethasone regimen and highly emetogenic chemotherapy requirement.

Does the patent require fosnetupitant?

No. The supplied claims recite netupitant, not fosnetupitant. A fosnetupitant product may be relevant because it generates netupitant after administration, but the patent does not expressly require the prodrug.

Can a generic avoid the patent by omitting dexamethasone from its label?

That may reduce inducement risk, but it does not automatically eliminate all exposure. Physicians may still prescribe dexamethasone, and the infringement analysis would depend on the proposed label, product use, evidence of induced conduct, and the interpretation of the combination-regimen limitation.

Are the 70% NK1 receptor-occupancy claims likely to be commercially decisive?

They are technically narrow and potentially difficult to prove. Their value may be greater as a litigation or settlement lever than as the primary standalone enforcement claims, unless the innovator has reliable pharmacodynamic evidence for the accused product.

Does this patent block all generic antiemetic combinations?

No. It is limited to regimens involving netupitant, palonosetron, and dexamethasone in the claimed CINV setting. Other NK1 antagonists, other 5-HT3 antagonists, or different chemotherapy-support regimens may fall outside its literal scope.

References

1. U.S. Patent No. 10,828,297. (2020). United States Patent and Trademark Office.

2. U.S. Food and Drug Administration. (2024). Akynzeo prescribing information. FDA.

3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.

4. U.S. Food and Drug Administration. (2024). Hatch-Waxman amendments and abbreviated new drug applications. FDA.

5. U.S. Patent and Trademark Office. (2024). Patent term adjustment and patent term extension resources. USPTO.

Drugs Protected by US Patent 10,828,297

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Helsinn Hlthcare	AKYNZEO	netupitant; palonosetron hydrochloride	CAPSULE;ORAL	205718-001	Oct 10, 2014		RX	Yes	Yes						USE IN COMBINATION WITH DEXAMETHASONE IN ADULTS FOR THE PREVENTION OF ACUTE AND DELAYED NAUSEA AND VOMITING ASSOCIATED WITH INITIAL AND REPEAT COURSES OF CANCER CHEMOTHERAPY, INCLUDING, BUT NOT LIMITED TO, HIGHLY EMETOGENIC CHEMOTHERAPY
Helsinn Hlthcare	AKYNZEO	fosnetupitant chloride hydrochloride; palonosetron hydrochloride	POWDER;INTRAVENOUS	210493-001	Apr 19, 2018		DISCN	Yes	No						USE IN COMBINATION WITH DEXAMETHASONE IN ADULTS FOR THE PREVENTION OF ACUTE AND DELAYED NAUSEA AND VOMITING ASSOCIATED WITH INITIAL AND REPEAT COURSES OF HIGHLY EMETOGENIC CANCER CHEMOTHERAPY
Helsinn Hlthcare	AKYNZEO	fosnetupitant chloride hydrochloride; palonosetron hydrochloride	SOLUTION;INTRAVENOUS	210493-002	May 27, 2020		RX	Yes	Yes						USE IN COMBINATION WITH DEXAMETHASONE IN ADULTS FOR THE PREVENTION OF ACUTE AND DELAYED NAUSEA AND VOMITING ASSOCIATED WITH INITIAL AND REPEAT COURSES OF HIGHLY EMETOGENIC CANCER CHEMOTHERAPY

International Family Members for US Patent 10,828,297

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
African Regional IP Organization (ARIPO)	3083
Australia	2010320598
Brazil	112012011485